Wnt signaling is key to several important processes, both in health and disease. The genes encoding the Wnt ligand and its receptor Frizzled have undergone extensive duplications during evolution, but how vertebrate cells are able to “decode” their 19 Wnt ligands and therefore make a variety of functions emerge from this genetic diversity was still largely unknown.

In “A molecular mechanism for Wnt ligand-specific signaling”, published this summer in Science, our colleague Benoit Vanhollebeke, his team and collaborators from the UCL NanoBiophysics Lab and Max Planck Institute for lung and heart research found some important pieces of the puzzle of Wnt signaling diversity. They dissect the molecular mechanism for Wnt7-specific signaling and unravel the central role played by Reck, GPR124 and Dishevelled the process. It can be hypothesized that other Wnt or Frizzled family members are decoded in a similar manner through other accessory proteins.

Image analysis is one of the strong points of our digital pathology team DIAPath. In a recent article, our colleagues at DIAPath explain how they used deep learning and data augmentation techniques to automate annotation of histological slide images from colorectal tissue. Their method segments glandular epithelium in images from tissue slides stained with hemaetoxylin & eosin or by immunohistochemistry (IHC). It is robust, outperforms pre-existing methods and concurs highly with manual annotations, thereby enabling the compatimentalization of IHC quantification.

What an exciting year! Many articles that benefited from the team and/or infrastructure of the CMMI were published in the last months. Some of them are below. A special focus on two additional CMMI articles will follow in the coming days. Congratulations to our collaborators for the good work!

Great news! We’ve been selected as finalist in the “Supporting smart industrial transition” category for the RegioStars 2018.
RegioStars are European awards that identify good practices in regional development and highlight original and innovative projects that are attractive and inspiring to other regions.

We are very proud to have been selected, and thankful to all our partners, especially to the Biopark and to the Walloon Region!

The plasma membrane of eukaryotic cells is compartmentalized into domains enriched in specific lipids and proteins. However, our understanding of the mechanisms and functions of this lateral segregation remains incomplete. In this study led by Christos Gournas from the Molecular Physiology of the Cell lab (ULB), we report that the clustering of the yeast Can1 arginine transporter into domains is dictated by its conformation and requires sustained biogenesis of complex sphingolipids. Furthermore, this clustering confers to Can1 and other transporters protection from ubiquit-independent endocytosis. Under nutrient starvation conditions, this protective role is reinforced, thereby allowing cells to preserve a fraction of their nutrient transporters from bulk endocytosis and to more efficiently resume growth when replenishing compounds are available. Our study reveals nutrient-regulated protection from endocytosis as an important role for protein partitioning into membrane domains.The images above were acquired on the CMMI’s Zeiss LSM710, using its Airy Scan module. Shown are surface section of an art1Δ bul1/2Δ gap1Δ can1Δ PIL1-mCherry yeast strain expressing Can1-GFP, Can1(T180R)-GFP, or Can1(S176N,T456S)-GFP. Can1(T180R) is a loss-of-function mutant of Can1 that is unable to bind Arg. Can1(S176N,T456S) is a mutant converted into a Lys-scpecific transporter. Taken together with additional data in the article, these observations demonstrated that substrate transport abolishes Can1 EMC clustering. Conditions and quantifications (n = 32–42) are as in B. ***P < 0.001; ns, nonsignificant, P > 0.05. (Scale bar: 2 μm.).

Inhaled chemotherapy for the treatment of lung tumors requires that drug delivery systems improve selectivity
for cancer cells and tumor penetration and allow sufficient lung residence. The study led by Rémi Rosière from the Laboratoire de Pharmacie Galénique et Biopharmacie demonstrates the positive impact of using coated “solid lipid nanoparticles” on the delivery of paclitaxel by inhalation.The CMMI’s contribution to the study was to image solid lipid nanoparticles by transmission electron microscopy. The figure above compares the morphology of paclitaxel-loaded solid lipid nanoparticles with or without F-PEG-HTCC coating. Scale bar: 200 nm.

In this collaborative clinical study, researchers from three hospitals (Erasme hospital in Brussels, André Vésale Hospital in Charleroi and Hôtel Dieu de France Hospital in Beirut) as well as from the CMMI investigate the relationship between the IL-8 cytokine and prostate cancer. They conclude that IL-8 serum level is not a significant predictor of diagnosis, aggressiveness or prognosis of prostate cancer.

Cancer research is increasingly dependent of patient-derived xenograft model (PDX). However, a major point of concern regarding the PDX model remains the replacement of the human stroma with murine counterpart. The present study investigates this issue in PDX models of colorectal cancer and liver metastasis, with an approach combining metabolomics (MALDI imaging) and the measurement of glucose uptake by in vivo PET. The data show for the first time that CRC/CRC-LM PDX model maintains the functional stability at the metabolic level despite the early replacement of the human stroma by murine cells. The findings demonstrate that human cancer cells actively educate murine stromal cells during PDX development to adopt the human-like phenotype.